1-46613059-G-T

Variant names:

• chr1-46613059-G-T
• rs757674170
• NM_201403.3:c.263C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_201403.3(MOB3C):​c.263C>A​(p.Pro88Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: MOB3C NM_201403.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.99

Genes affected

MOB3C (HGNC:29800): (MOB kinase activator 3C) The protein encoded by this gene is similar to the yeast Mob1 protein. Yeast Mob1 binds Mps1p, a protein kinase essential for spindle pole body duplication and mitotic checkpoint regulation. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

MKNK1 (HGNC:7110): (MAPK interacting serine/threonine kinase 1) This gene encodes a Ser/Thr protein kinase that interacts with, and is activated by ERK1 and p38 mitogen-activated protein kinases, and thus may play a role in the response to environmental stress and cytokines. This kinase may also regulate transcription by phosphorylating eIF4E via interaction with the C-terminal region of eIF4G. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.882

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOB3C	NM_201403.3	c.263C>A	p.Pro88Gln	missense_variant	Exon 2 of 4	ENST00000319928.9	NP_958805.1
MOB3C	NM_145279.5	c.263C>A	p.Pro88Gln	missense_variant	Exon 2 of 4		NP_660322.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOB3C	ENST00000319928.9	c.263C>A	p.Pro88Gln	missense_variant	Exon 2 of 4	2	NM_201403.3	ENSP00000315113.3
MOB3C	ENST00000271139.13	c.263C>A	p.Pro88Gln	missense_variant	Exon 2 of 4	1		ENSP00000271139.9
MOB3C	ENST00000371940.1	c.263C>A	p.Pro88Gln	missense_variant	Exon 1 of 3	1		ENSP00000361008.2
MKNK1	ENST00000531769.6	c.-171+3652C>A		intron_variant	Intron 1 of 4	4		ENSP00000434021.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461762 Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10 AN XY: 727200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000180

Gnomad4 OTH exome AF: 0.0000662

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000312 Hom.: 0

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;T;T
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D;D;.
M_CAP	Benign	0.0075	T
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Pathogenic	3.0	M;.;M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-7.3	D;D;.
REVEL	Pathogenic	0.71
Sift	Pathogenic	0.0	D;D;.
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.87
MutPred		0.74		Loss of glycosylation at S86 (P = 0.0574);.;Loss of glycosylation at S86 (P = 0.0574);
MVP		0.67
MPC		1.2
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.83
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs757674170; hg19: chr1-47078731;